Linked Life Data

8971426

Source:http://linkedlifedata.com/resource/pubmed/id/8971426

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1997-3-19
pubmed:abstractText
1. The debrisoquine hydroxylase (CYP2D6) is polymorphically distributed. Not only are there differences in the proportions of extensive metabolisers to poor metabolisers in various ethnic groups, but there are also pronounced variations in the metabolic capacity among those classified as extensive metabolisers. 2. The mean debrisoquine metabolic ratio of Caucasian extensive metabolisers is lower than that for a number of African populations. In the present study, we have searched for novel CYP2D6 mutations to explain the diminished enzyme activity in African populations. 3. Three Zimbabwean Shona subjects with EM phenotypes (metabolic ratios for debrisoquine of 0.4, 1.5 and 10.5 respectively) were selected and the open reading frame of the CYP2D6 gene of each was sequenced. 4. The subject with metabolic ratio of 10.5 was found to be homozygous for an allele with a nucleotide exchange in exon 2, 1111C-->T causing a 107Thr-->Ile amino acid exchange in a conserved region of the enzyme. In addition, he was homozygous for the 2938C-->T and 4268G-->C mutations causing 296Arg-->Ser and 486Ser-->Thr amino acid substitution found in the CYP2D6*2 allele. 5. Seventy-six Zimbabwean Shona subjects were subsequently genotyped for the 1111C-->T mutation and for the intron 1 gene conversion present in the CYP2D6*2 gene. The 1111C-->T mutation was found at an allele frequency of 34% and was only present in alleles carrying the gene conversion in intron 1 indicative for the CYP2D6*2 gene. 6. This allele (CYP2D6*17), containing the 1111C-->T, 2938C-->T and 4268G-->C mutations, was found to be strongly associated with lower capacity for debrisoquine hydroxylation. We therefore postulate that the CYP2D6*17 allele might contribute to the molecular basis of the previously established diminished debrisoquine hydroxylase activity in African Bantu populations.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0306-5251
pubmed:author
pubmed:issnType
Print
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
713-9
pubmed:dateRevised
2009-10-2
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity.
pubmed:affiliation
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't